p53,PCNA在口腔粘膜癌前病变中的表达及其临床意义

目的观察ｐ５３和ＰＣＮＡ在口腔粘膜癌前病变中的表达特征,进一步探讨其临床意义。方法对５０例临床疑为癌前病变的患者行局部组织活检、光镜检查,作出病理诊断;同时采用免疫组织化学方法进行ｐ５３和ＰＣＮＡ的标记,并将两者结果做比较。结果在癌前病变中,随着上皮细胞的异常增生从基底层向角化层发展,ｐ５３和ＰＣＮＡ阳性表达细胞也随着同步发展。病变伴不同程度异常增生的各病例阳性表达程度之间有显著差异（Ｐ＜０．０１）。结论ｐ５３和ＰＣＮＡ在口腔粘膜癌前病变中的表达呈同步性。且与病变细胞的异常增生程度呈正相关;ｐ５３在癌前病变中的阳性表达可能是其发生癌变的早发事件;癌变的发生可在上皮异常增生的较早期。故ｐ５３和ＰＣＮＡ的检测有利于临床上早期发现有异常增生倾向的病变。     

增殖细胞核抗原及P53在舌癌中的表达

目的：研究ＰＣＮＡ、Ｐ５３在舌癌中表达的相关性及与肿瘤病理分级、淋巴结转移、预后的关系。方法：应用免疫组化ＳＰ法，观察４６例病理确诊的舌癌石蜡标本中ＰＣＮＡ指数及Ｐ５３阳性率的表达。结果：ＰＣＮＡ在所有病例均有不同程度表达，４６例中２８例呈Ｐ５３阳性表达（６０．９％）。Ｐ５３阳性组中ＰＣＮＡ指数明显高于Ｐ５３阴性组（Ｐ＜０．００１）。ＰＣＮＡ指数随舌癌病理分级的升高而增加（Ｐ＜０．０２５）。Ｐ５３阳性率在Ⅱ、Ⅲ级舌癌明显高于Ⅰ级舌癌（Ｐ＜０．０５）。在有淋巴结转移及术后生存小于３年组中ＰＣＮＡ指数及Ｐ５３阳性率均明显高于无淋巴结转移及术后生存３年以上组（Ｐ＜０．００１，Ｐ＜０．０５）。结论：联合检测ＰＣＮＡ及Ｐ５３对判断舌癌恶性度，预测淋巴结转移趋势和预后及指导临床治疗有重要价值。     

PCNA,p53在口腔粘膜癌前病变及鳞癌中表达的免疫组化研究

应用免疫组化方法对３９例口腔粘膜癌前病变和癌中的增殖细胞核抗原，突变型ｐ５３的表达进行检测。结果表明：从ＬＰ，ＬＫ到ＩＳＣ，其ＰＣＮＡ和Ｐ５３的阳性表达均呈递增趋势。提示ＰＣＮＡ，Ｐ５３表达程度与细胞增殖程度和分化程度关系密切。     

DMBA诱导的金黄地鼠颊囊癌变粘膜中增殖细胞核抗原表达

实验采用抗增殖细胞核抗原单克隆抗体对１０９例金黄地鼠颊囊粘膜标本作免疫组化染色及网格计数和形态学观察，发现正常的金黄地鼠颊囊粘膜基底层有少量增殖细胞核抗原（ＰＣＮＡ）阳性细胞，而上皮异常增生以及癌变时，随着病变程度的加重，ＰＣＮＡ阳性细胞率也相应增加。统计学分析显示：正常粘膜各级上皮异常增生以及癌变各组间ＰＣＮＡ阳性细胞率有显著差异（Ｐ＜０．０５），轻度上皮异常增生组中涂ＤＭＢＡ６周与７周的ＰＣＮＡ阳性分级有显著性差异（Ｐ＜０．０５）；涂ＤＭＢＡ７周，８周，９周之间，其ＰＣＮＡ阳性分级无差异（Ｐ＞０．０５），提示ＰＣＮＡ可作为动态观察癌前病变过程中细胞增殖程度的一种检测指标，它的敏感性强于光镜形态学观察。     

增殖细胞核抗原和抑癌基因P53在粘液表皮样癌中的表达

为对粘液表皮样癌中增殖细胞核抗原（ｐｒｏｌｉｆｅｒａｔｉｎｇｃｅｌｎｕｃｌｅａｒａｎｔｉｇｅｎ，ＰＣＮＡ）和Ｐ５３蛋白的表达及分布特点进行分析，作者采用免疫组织化学过氧化物酶法对４１例粘液表皮样癌进行了研究。所有病例均有ＰＣＮＡ阳性表达，ＰＣＮＡ表达指数和染色强度与肿瘤组织学分级呈正相关。根据ＰＣＮＡ阳性细胞分布情况可分为３种类型，分布类型与肿瘤组织学分级相一致。Ｐ５３蛋白总阳性率为４１．５％，除外偶见Ｐ５３阳性细胞９例，阳性率为１９．５％。结果提示：Ｐ５３蛋白在粘液表皮样癌中表达率较低。ＰＣＮＡ表达指数和染色强度可作为评价粘液表皮样癌分化程度的生物学指标。ＰＣＮＡ阳性细胞分布类型有助于粘液表皮样癌的病理学分级诊断     

增殖细胞核抗原和p53蛋白在涎腺肿瘤中的表达

为了研究增殖细胞核抗原（ｐｒｏｌｉｆｅｒａｔｉｎｇｃｅｌｎｕｃｌｅａｒａｎｔｉｇｅｎ，ＰＣＮＡ）和ｐ５３在涎腺肿瘤中的表达，作者用抗ＰＣＮＡ及ｐ５３单克隆抗体对良、恶性混合瘤及粘液表皮样癌组织标本进行了免疫组化染色。结果表明，恶性混合瘤ＰＣＮＡ增殖指数较高，与混合瘤细胞生长活跃型及混合瘤相比差异有极显著性（Ｐ＜０．０１）；低分化粘液表皮样癌的ＰＣＮＡ阳性表达明显高于高分化型（Ｐ＜０．０１）。ｐ５３在恶性混合瘤中阳性表达率高（６０．０％），与粘液表皮样癌（２０．０％）相比差异有显著性（Ｐ＜０．０５）。另外，我们观察到ｐ５３阳性表达的肿瘤组织ＰＣＮＡ增殖指数较高。结论：ＰＣＮＡ增殖指数可以作为支持诊断恶性混合瘤的指标；是粘液表皮样癌组织学分级的重要参数。ｐ５３蛋白是恶性混合瘤的有效标记物；ｐ５３蛋白参与ＰＣＮＡ表达的调节。     

复方绞股蓝对金地鼠颊囊部变过程的PCNA变化的影响

实验采用免疫组化技术，以增殖细胞核抗原（ＰＣＮＡ）为检测指标，对复方ＧＰ阻断金地鼠颊囊癌前病变的作用进行观察，发现复方ＧＰ能有效地降低ＰＣＮＡ阳性细胞标识库，与模型对照相比，有显著性差别。说明复方ＧＰ通过抑制细胞异常增殖而发挥阻癌抑癌效果。     

口腔粘膜上皮癌变过程中增殖细胞核抗原改变研究

采用抗增殖细胞核抗原单克隆抗体对５８例标本进行了免疫组化染色，结果显示：正常口腔粘膜基底细胞层可有少量ＰＣＮＡ阳性细胞，而上皮异常增生及鳞癌时，随着病变程度的加重，ＰＣＮＡ阳性表达也相应提高，统计学分析，各组间有显著差异（Ｐ＜０．０５）。提示：ＰＣＮＡ表达对判断口腔癌前病变的增殖活动有一定意义。     

口腔粘膜上皮癌前及癌变中PCNA和P53的表达

目的：检测口腔粘膜上皮癌前及癌变组织中ＰＣＮＡ和ｐ５３的表达，探讨口腔癌变的机理。方法：采用免疫组化的方法检测８０例口腔粘膜病变组织中ＰＣＮＡ和ｐ５３的表达。结果：正常口腔粘膜基底层有少数ＰＣＮＡ阳性细胞，随着粘膜异常增生程度的加重到鳞癌，ＰＣＡＮ表达的阳性分级升高，ＰＣＮＡ的相对含量也升高。Ｐ５３的阳性表达仅见于重度异常增生及鳞癌组织中。结论：对ＰＣＮＡ和ｐ５３的研究有助于探讨口腔粘膜癌变多阶段发生过程的机理，并可为监测癌变提供生物学指标。     

口腔鳞癌细胞增殖核抗原和P53免疫组化的比较研究

本文运用ＡＢＣ免疫组化结合图象分析，定量分析了ＰＣＮＡ（细胞增殖核抗原）和Ｐ５３在口腔鳞癌中的表达。探讨了两者在口腔鳞癌的临床病理、肿瘤侵龚和转移等方面的异同点。结果表明：ＰＣＮＡ的表达强度和阳性率与肿瘤的病理分级有关，与肿瘤细胞的侵龚转换无关。而Ｐ５３和肿瘤细胞的侵龚有关密切的关系（Ｐ〈０．０５）。Ｐ５３阳性者，淋巴结转移率较高（８０％）。结果表明在口腔鳞癌的临床行为恶性，预后等方面定量分析上述     

口腔癌前病变和鳞癌P53表达与微核的关系

目的：分析脱落细胞涂片和组织病理切片检测P53蛋白水平的意义,探讨P53表达与微核的关系,方法：对20例白斑和18例癌患者的口腔粘膜脱落细胞涂片和组织病理切片进行P53表达的免疫组化研究,对脱落细胞涂片还进行计数的分析,结果：组织切片中,P53表达阳性率在上皮异常增生白斑中为60％,在上皮单纯增生白斑中为10％（P＜0．05）,P53蛋白表达阳性组和阴性组织胸微核数无显著性差异。结论：P53蛋白的过表达从肿瘤发生的早期阶段就开始出现,与上皮增生的程度有正相关性,微核计数升高是肿瘤发生中更早期的事件。     

P53 expression and clinical significance in oral squamous cell carcinoma]

P53 protein expression was investigated in oral squamous cell carcinomas and oral premalignant lesions by monoclonal antibody Do-1 and immunohistochemistry technique. 4 of 12 (33.3%) samples of severe epithelial dysplasia and 25 of 44 (56.8%) samples of squamous cell carcinoma expressed P53 protein while all the normal mucosa, mild and moderate epithelial dysplasia were negative. The P53 expression in carcinomas was associated with differentiation, lymph node metastasis and tumour stage. This result indicated that P53 genic mutation might be an early event in oral mucosa carcinogenesis and related to oral tumor progression. Detection of P53 protein probably has clinical significance in identifying the premalignant lesions of oral mucosa and predicting the prognosis of oral carcinomas.     

c—myc,P53,Bcl—2和人类乳头状与涎腺肿瘤的关系

本文采用免疫组化、PCR技术，检测30例涎腺肿瘤组织中c－myc、P53、Bcl－2蛋白表达和HPV感染。结果显示：多形性腺瘤中，c－myc和P53阳性率分别为50．0％和25．0％，均低于恶性肿瘤阳性率的75．0％和50．8％，两组存在高度显著性差异（P＜0．01）；15例多形性腺瘤和3例鳞癌中，HPV6．11均为阴性，HPV16．18阳性反应各1例（1／15和1／3）。提示c－myc表达升高，与上皮细胞增殖速度加快及细胞癌变有关；P53蛋白表达，可为判断细胞分化程度的参考指标；HPV16．18具一定协同致癌作用。Bcl－2能引起细胞过度积聚，故为恶性肿瘤的发病机制之一。     

p53 protein expression in sequential biopsies of oral dysplasias and in situ carcinomas

Immunohistochemically detectable levels of p53 may be seen early in the malignant transformation of some neoplasms. To determine if p53 is immunocytochemically detectable, and therefore presumptively abnormal, in oral dysplasias and in situ carcinomas, and to explore the natural history of p53 protein expression in these lesions, sequential biopsies from patients with lesions occurring in the same anatomic site were examined. Formalin-fixed, paraffin-embedded sections from 19 patients were evaluated immunohistochemically for p53 protein using antibody clones Pab1801 and BP53-12. With two exceptions, comparable results were observed with these antibodies. p53 protein was detected immunocytochemically in 6 of 13 patients with dysplasias; 3 of these progressed to p53-positive invasive carcinoma, one advanced to a more severe grade of p53-positive dysplasia, one developed into a p53-negative verrucous carcinoma, and one represented a p53-positive dysplasia developing five years after treatment of a p53-positive carcinoma. The p53-positive dysplasias, which were found in all subtypes (mild, moderate, severe), preceded histologic malignant change by months to years. p53 detection was evident in 4 of 6 patients with in situ lesions. Sequential biopsies of three of these lesions showed no change in lesion histology or p53 staining, and one lesion advanced to a p53-positive carcinoma. It is concluded that p53 protein may be detected early in the development of a subset of p53-positive oral squamous cell carcinomas. This phenomenon may be seen in dysplasias and in situ lesions, and it may have prognostic implications.     

Expression of p53 in oral mucosal hyperplasia, dysplasia and squamous cell carcinoma

OBJECTIVE: To assess p53 expression in a range of oral mucosal lesions and to relate the results to the clinical outcome in patients with dysplastic oral mucosal lesions and oral squamous cell carcinomas (OSCC).
MATERIALS AND METHODS: Archival tissue was available for eight cases of normal oral mucosa, 50 cases of oral mucosal hyperplasia, 41 cases of oral mucosal dysplasia and 48 cases of OSCC. The monoclonal antibody DO-7, reactive to p53 protein, was applied to paraffin-embedded sections using microwave pretreatment and immu-nohistochemical techniques.
RESULTS: The results showed that normal oral mucosa did not express p53.Positive nuclear staining was found in 18/50 (36%) cases of hyperplasia, 35/41 (85%) cases of dysplasia and 45/48 (94%) cases of OSCC.None of the p53 negative dysplasias progressed, while 19% of p53 positive cases of dysplasia recurred following excision and 11% of the cases underwent neoplastic transformation. Five out of 10 (50%) cases of severe dysplasia which were p53 positive resolved.
CONCLUSION: The proportion of cases with positive p53 expression increased from hyperplasia to dysplasia to OSCC. These results may indicate an involvement of p53 in neoplastic transformation as well as in proliferative events although the presence or absence of p53 staining could not be used to predict the outcome of potentially malignant oral mucosal lesions.     

Higher expressions of p53 and proliferating cell nuclear antigen (PCNA) in atrophic oral lichen planus and patients with areca quid chewing

OBJECTIVE: The aim of the study was to examine the expressions of p53 and proliferating cell nuclear antigen (PCNA) in oral lichen planus (OLP) in relation to its clinical behavior and the patients' oral habits. STUDY DESIGN: Immunohistochemical study was carried out to investigate the expressions of p53 and PCNA in 56 OLP specimens. The results were correlated with the clinical behavior of the disease and the patients' oral habits. The expression rates were further compared with those of normal oral mucosa (NOM), epithelial hyperkeratosis (EH), epithelial dysplasia (ED), and squamous cell carcinoma (SCC). RESULTS: The staining rate of p53 (28.6%) and PCNA labeling index (LI) (27.6 +/- 8.8%) in OLP were similar to those in EH ( P = .868, .074, respectively), but higher than those of NOM and lower than those of ED and SCC (all P < .05). In OLP, no significant correlations were found between p53 or PCNA expression and the patients' age, gender, lesion duration, location, size, number of site, presence of pain, presence of local irritant, and the habits of alcohol drinking and cigarette smoking (all P > .05). In addition, the mean PCNA LI of p53+ cases was close to that of p53- cases (P = .38). However, the staining rate of p53 in OLP was higher in areca quid (AQ) chewers compared to abstainers (P = .001), and the mean PCNA LI in atrophic cases was higher than that in hypertrophic cases (P = .029). Interestingly, the staining rate of p53 and mean PCNA LI were significantly increased in AQ chewers with atrophic OLP (100%, 36.7% +/- 9.0%, respectively), which were similar to those in ED and SCC (all P > .05). CONCLUSIONS: Although this study could not confirm the precancerous nature of OLP by the relatively low p53 and PCNA expression, the results do suggest that atrophic form OLP and patients with AQ chewing habit may have a higher disease activity in view of higher expression rates of p53 and PCNA in the lesions.     

p53 protein and Ki-67 reactivity in epithelial odontogenic lesions. An immunohistochemical study

Forty-five examples of epithelial odontogenic lesions (9 ameloblastomas (AB): 13 odontogenic keratocysts (OKC): 15 dentigerous cysts (DC): 6 radicular cysts (RC): and 2 odontogenic carcinomas (OC)) were immunohistochemically analyzed for the presence of p53 protein (p53P) and proliferative activity as indicated by positivity for Ki-67 antigen. p53P⁺ cells, detected as dense and/or faint nuclear staining, were found in 42 of the 45 odontogenic lesions examined. Dense p53P reactivity was most commonly detected in OKC, AB and OC, with other lesions generally exhibiting only weak nuclear reactivity. Numbers of Ki-67 positive cells as well as p53P⁺ cells were scored semiquantitatively. Although the presence/absence of densely stained p53P⁺ cells was broadly related to Ki-67⁺ cell numbers, there were no differences in p53P⁺ cell numbers between lesions exhibiting differences in proliferative activity. These results suggest that overexpression of p53P, rather than increased numbers of p53P⁺ cells, is related to proliferation in odontogenic epithelial lesions.     

Immunohistochemical analysis of the p53 tumor suppressor gene product in oral leukoplakia

Squamous Cell Carcinoma (SCC) is the most frequent malignancy in the oral cavity. p53 protein has been reported to be expressed at high levels in malignant lesions, while the level in premalignant lesions has yet to be determined. In this study, oral leukoplakia and oral SCC were examined. Seventy-four incision or excision samples from 43 cases diagnosed as leukoplakia, and 41 samples from 37 SCC cases in the oral cavity, were obtained. All samples (formalin-fixed, paraffin embedded) were examined immunohistochemically for overexpression of p53 protein with monoclonal antibody BP 53-12. As the result, 1. Twenty-two out of 43 leukoplakia cases, and 29 out of 37 oral SCC cases, were positive for p53 protein. 2. p53 protein was overexpressed in premalignant lesions, especially in the cases with moderate and severe epithelial dysplasia. 3. There was a relation between p53 protein expression and pathological features of leukoplakia (epithelial dysplasia), statistically. 4. There was a relation between p53 protein expression and clinical features of leukoplakia, statistically. 5. Malignant transformation during clinical observation was seen in 11 cases. Nine out of 11 cases were positive for p53 even before malignant transformation. Since in cancer-development cases, p53 staining was detected even before malignant transformation of oral leukoplakia to squamous cell carcinoma, it is indicated that p53 accumulation occurred at a early stage of cancer-development. In conclusion, immunohistochemical analysis of p53 protein is suggested to be useful diagnostic procedure for oral leukoplakia, which may develop into oral SCC.     

P53蛋白在口腔鳞状细胞癌发生过程中的表达及意义

本研究采用微波处理暴露抗原,通过免疫组化ＬＳＡＢ方法对ＮＯＭ６例,ＯＰＬ２８例,ＯＳＣＣ３４例中Ｐ５３蛋白表达进行观察,其ＮＯＭ无表达;在ＯＰＬ中的表达率为８２％随着上皮异常增生的程度加重,表达率呈上升趋热（Ｐ〈０．０５）;而在ＯＳＣＣ中表达率为６５％,随着肿瘤的分极增加,表达率呈下降趋势（Ｐ〈０．０５）。结果表明,Ｐ５３蛋白在ＯＰＬ和ＯＳＣＣ中呈异常表达,并与ＯＰＬ程度和ＯＳＣＣ分级有关,Ｐ５３     

Cytoplasmic expression of p53 protein and its morphological features in salivary gland lesions

An immunohistochemical study of p53 protein was carried out on 45 salivary gland lesions using a monoclonal antibody, Bp53–12, raised to the intracellular domain of the p53 protein. p53 protein expression was found in 34.4% of 32 salivary gland carcinomas. Nuclear p53 expression was detected in tumor cells but not in non-neoplastic cells, except in one salivary duct carcinoma. The perinuclear cytoplasm of luminal duct cells was specifically positive for the antibody used here. Cytoplasmic p53 expression was observed mostly in non-neoplastic cells. There was a tendency for the Cytoplasmic staining of p53 protein to be observed in the normal cells adjacent to p53-positive carcinomas, but none of the normal cells were positive in the tissues surrounding p53-negative carcinomas. Cytoplasmic expression of p53 protein in salivary gland tissues seems to be correlated with tumorigenesis.